Cdk1, Plks, Auroras, and Neks: the mitotic bodyguards.
Cdk1, Plks, Auroras, and Neks: the mitotic bodyguards.
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DOI：
10.1007/978-0-387-69080-3_4
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发表时间：
2008
影响因子：
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通讯作者：
P. Salaun;Yoann Rannou;C. Prigent
中科院分区：
文献类型：
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作者：
P. Salaun;Yoann Rannou;C. Prigent
1858年，细胞生物学中的一个重要教条诞生了，鲁道夫·魏尔肖（Rudolf Virchow）认为每个细胞都必须来自一个预先存在的细胞。事实上，细胞分裂是生命消耗的唯一方式，也是永生的方式，不幸的是，如果不受控制，也是癌症的方式。但是导致细胞分裂的不为人知的机制花了相当长的时间。一个母细胞如何分裂产生两个女儿？这就是所谓的细胞周期，它描述了一系列确保遗传信息从一代细胞到下一代细胞忠实过渡的事件。这些分裂机制在整个进化过程中一直保持不变;它们是所有生物体生长和发育的基础，也是它们遗传和进化的核心。在真核细胞中，细胞周期首先被描述为两个不同的阶段：间期和细胞分裂之前的有丝分裂（图1）。间期分为3个阶段，S期代表DNA合成期，G1和G2期代表Gap期。有丝分裂在1882年由沃尔特·弗莱明（Walter Flemming）充分描述，它仍然是细胞周期中最壮观和最复杂的部分。在不到一个小时的时间里，母细胞组织了一个复杂的机器，旨在将其遗传信息和所有亚细胞成分分离成两个相同的集合，由两个子细胞继承。如果有丝分裂没有任何错误地进行，它最终以胞质分裂结束，对应于两个子细胞的物理分离。1902年，Theodor Boveri预测有丝分裂过程中的错误是癌症的起源。一百年后，科学界仍在争论这是否是真的。有丝分裂进程的协调主要是由几种丝氨酸/苏氨酸激酶所确保的蛋白质磷酸化来协调的。在这篇简短的综述中，我们将重点介绍四个主要的有丝分裂激酶家族：细胞周期蛋白依赖性激酶：Cdks，polike激酶：Plks，Aurora激酶和NIMA相关激酶：Neks。“细胞周期蛋白依赖性激酶”，即必须与细胞周期蛋白结合以成为活性激酶的Cdk，是细胞周期进程的关键调节因子。现在大约有12个Cdk;第一个Cdk 1（或cdc 2）长期以来被认为是细胞周期主激酶，被认为负责所有细胞周期转换（1）。这是真
“Omnis cellula e cellula,” in 1858, an important dogma in cell biology was born, when Rudolf Virchow established that every cell must derive from a preexisting cell. And indeed cell division is the only way for life to expend, it is also the way for immortalization, and unfortunately when uncontrolled also the way for cancer. But unrevealing mechanisms leading to cell division took quite a while. How does a mother cell divide to give two daughters? This is known as the cell cycle, which describes a series of events that insures faithfully transition of the genetic information from one cell generation to the next. These dividing mechanisms have been conserved throughout evolution; they underlie growth and development in all living organisms and are central to their heredity and evolution. In eukaryotic cells, the cell cycle was first described as two distinct phases: interphase and mitosis that just precedes cell division (Fig. 1). The interphase was later on divided into three phases, S-phase standing for DNA synthesis surrounded by two G-phases G1 and G2 standing for Gap-phases. Fully described by Walter Flemming in 1882, mitosis remains the most spectacular and sophisticated part of the cell cycle. In less than an hour, the mother cell organizes a complex machine aim to separate its genetic information and all its subcellular components into two identical sets that will be inherited by the two daughter cells. If mitosis proceeds without any error it eventually ends up with cytokinesis corresponding to the physical separation of the two daughter cells. Theodor Boveri predicted errors during mitosis to be at the origin of cancer in 1902. Hundred years later the scientific community is still debating on whether or not this might be true. The coordination of progression through mitosis is mainly orchestrated by protein phosphorylation insured by several serine/threonine kinases. In this short review we will focus on the four main mitotic kinase families: the cyclin-dependent kinase: Cdks, the pololike kinases: Plks, the Aurora kinases, and the NIMA-related kinases: Neks.“Cyclin-dependant kinases,” Cdks that must associate to a cyclin to become active kinases are key regulators of cell cycle progression. There are now about 12 Cdks; the first one Cdk1 (or cdc2) has long been considered as THE cell cycle master kinase, thought to be responsible for all cell cycle transitions (1). This is true